In December of 1262, he was made cardinal-priest (nominally in charge of the church of St. Cecilia) by Pope Urban VI.

He served as legate[?] for Urban VI and also for his successor Clement IV in the negotiations for the assumption of the crown of Sicily by Charles of Anjou, with whom he became deeply politically entwined. Later, Pope Gregory X sent him again as legate to stem the abuses of the Catholic Church there; there he presided over several synods on reform, the most important of which was held at Bourges in September, 1276.

Viterbo was placed under interdict[?] for the imprisonment of the cardinals, and Rome was not at all inclined to accept a hated Frenchman as Pope, so Simon was crowned instead at Orvieto on March 23, 1281. (Though he was only the second pope to choose the name of Martin, he is now known as Martin IV, because the Popes Marinus I and Marinus II have historically been listed among the Martins.)

Dependent on Charles of Anjou in nearly everything, the new Pope quickly appointed him to the position of Roman Senator[?]. At the insistence of Charles, Martin IV excommunicated the Byzantine emperor Michael VIII Palaeologus, who stood in the way of Charles' plans to restore the Latin Empire of the East. He thus broke the tenuous union which had been reached between the Greek and the Latin Churches at the Council of Lyons[?] in 1274, and further compromise was rendered impossible.

In 1282, Charles was overthrown in the violent massacre known as the Sicilian Vespers[?]. The Sicilians had elected Peter III of Aragon as their king, but Martin IV used all the spiritual and material resources at his command against him, trying to preserve Sicily for France. He excommunicated Peter III, declared his kingdom of Aragon forfeit, and ordered a crusade against him, but it was all in vain.